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ETS1 and PAX5 transcription factors recruit AID to Igh DNA
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
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2018 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 10, p. 1687-1697Article in journal (Refereed) Published
Abstract [en]

B lymphocytes optimize antibody responses by class switch recombination (CSR), which changes the expressed constant region exon of the immunoglobulin heavy chain (IgH), and by somatic hypermutation (SH) that introduces point mutations in the variable regions of the antibody genes. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates both these antibody diversification processes by deaminating cytosine to uracil. Here we asked the question if transcription factors can mediate the specific targeting of the antibody diversification by recruiting AID. We have recently reported that AID is together with the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus. Here we report that also ETS1 is together with AID in this complex on key sequences of the Igh locus in splenic B cells of mice. Furthermore, we show that both ETS1 and PAX5 can directly recruit AID to DNA sequences from the Igh locus with the specific binding site for the transcription factor. Taken together, our findings support the notion of a targeting mechanism for the selective diversification of antibody genes with limited genome wide mutagenesis by recruitment of AID by PAX5 and ETS1 in a transcription factor complex.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018. Vol. 48, no 10, p. 1687-1697
Keywords [en]
Activation-induced cytidine deaminase, Class switch recombination, Protein interactions, Somatic hypermutation, Transcription factors
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-152886DOI: 10.1002/eji.201847625ISI: 000446431600008PubMedID: 30089192OAI: oai:DiVA.org:umu-152886DiVA, id: diva2:1259819
Funder
Swedish Cancer SocietySwedish Research CouncilAvailable from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-10-31Bibliographically approved

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Grundström, ChristineKumar, AnjaniPriya, AnshuNegi, NeemaGrundström, Thomas

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